Exhaled Nitric Oxide, Lung Function, and Exacerbations in Wheezy Infants and Toddlers

Background: There are limited data assessing the relationship between fraction of exhaled nitric oxide and lung function or exacerbations in infants with recurrent wheezing.

Objectives: In a longitudinal pilot study of children less than 2 years old, we assessed whether baseline fraction of exhaled nitric oxide was associated with lung function, bronchodilator responsiveness, changes in lung function, or subsequent exacerbations of wheezing.

Methods: Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 44 infants and toddlers (mean age, 15.7 months) with recurrent wheezing. Single-breath exhaled nitric oxide (SB-eNO) was measured at 50 mL/s. Lung function was again measured 6 months after enrollment.

Results: At enrollment, forced expiratory volume in 0.5 seconds (FEV(0.5)), forced expiratory flow at 25% to 75% of expiration (FEF(25-75)), and forced expiratory flow at 75% of expiration (FEF(75)) z scores for the cohort were significantly less than zero. There was no correlation between enrollment SB-eNO levels and enrollment lung function measures. SB-eNO levels were higher in infants with bronchodilator responsiveness (46.1 vs 23.6 ppb, P < .001) and was associated with a decrease in FEV(0.5) (r = -0.54, P = .001), FEF(25-75) (r = -0.6, P < .001), and FEF(75) (r = -0.55, P = .001) over 6 months. A 10-ppb increase in SB-eNO level was associated with a 0.4-point z score decrease in FEV(0.5), a 0.4-point z score decrease in FEF(25-75), and a 0.42-point z score decrease in FEF(75). SB-eNO level was superior to lung function and bronchodilator responsiveness in predicting subsequent wheezing treated with systemic steroids.

Conclusions: SB-eNO level might predict changes in lung function and risk of future wheezing and holds promise as a biomarker to predict asthma in wheezy infants and toddlers.